Exhaled nitric oxide: Not associated with asthma, symptoms, or spirometry in children with sickle cell anemia

Abstract

Background Significance of exhaled nitric oxide (FeNO) levels in children with sickle cell anemia (SCA) is unclear, but increased levels may be associated with features of asthma and thus increased morbidity. Objectives To determine factors associated with FeNO and whether FeNO levels are associated with increased rates of acute chest syndrome (ACS) and pain. Methods All participants had SCA, were part of the prospective, observational Sleep and Asthma Cohort study, and had the following assessments: FeNO, spirometry, blood samples analyzed for hemoglobin, white blood cell count, eosinophils and total serum IgE, questionnaires about child medical and family history, and review of medical records. Results The analytic sample included 131 children with SCA, median age 11.2 years (range 6-18) followed for a mean of 16.2 years, including a mean 5.1 years after the baseline FeNO data measurements. In multivariable analyses higher FeNO was associated with ln(IgE) (p<0.001), and the highest quartile of peripheral eosinophil count (p=0.03), but not wheezing symptoms, baseline spirometry indices, or response to bronchodilator. Multivariable analyses identified that incident rate of ACS was associated with ln(FeNO) (p=0.03) as well as male gender (p=0.025), wheezing causing shortness of breath (p=0.002), and ACS <4 years of age (p <0.001). FeNO was not associated with future pain episodes. Conclusions Steady state FeNO was not associated with an asthma diagnosis, wheezing symptoms, lung function measures, or prior sickle cell morbidity, but was associated with markers of atopy and increased risk of future ACS events.

Inhaled steroids reduce pain and sVCAM levels in individuals with sickle cell disease: A triple‐blind, randomized trial

“…There were no clinically meaningful changes in either group with eNO. This is consistent with the findings of Cohen et al in the Sleep and Asthma Cohort and suggests that eNO levels in patients with SCD may not be a marker of steroid responsive eosinophilic inflammation. The lack of difference between groups with spirometry was likely because individuals with asthma were screened out and most had normal spirometry at entry.…”

“…At study entry and 8‐weeks, assessments included ASCQ‐Me (NHLBI developed SCD quality of life measurement tool) pain domain, spirometry with bronchodilator, eNO, peripheral blood testing (standard‐of‐care tests and peripheral‐blood markers of inflammatory activation) and side‐effect questionnaires. Procedures for pulmonary function testing were identical to those used for the Sleep and Asthma Cohort and are included as a supplement. Adverse events were assessed for every hospital visit, via questionnaire at each in‐person assessment, and at follow‐up phone calls, which occurred at 2‐weeks, 4‐weeks and 12‐weeks.…”

“…Sickle mice demonstrate elevated airway inflammation, higher levels of pulmonary CD4+ and CD8+ T cells and myeloid activation chemokines . This inflammation does not appear to be driven exclusively by eosinophilic processes in humans as levels of exhaled nitric oxide (eNO) are only slightly higher in SCD compared with healthy controls but not as high as individuals with poorly controlled asthma . Given these data, anti‐inflammatory asthma therapies (oral leukotriene inhibitors and inhaled corticosteroids) are promising as adjuvant SCD therapy.…”

Salbutamol Worsens the Autonomic Nervous System Dysfunction of Children With Sickle Cell Disease

“…SCD children with asthma depicted a more severe disease according to the incidence of VOC and ACS. SCD patients with a diagnosis of asthma did not exhibit increased exhaled NO values, as previously demonstrated (Delclaux et al, 2005;Cohen et al, 2016). Asthmatic non-SCD children were characterized by an increase in exhaled NO that explained the relationship between bronchodilator response and exhaled NO, as previously evidenced (Mahut et al, 2010).…”

Airway inflammation in sickle cell disease—A translational perspective

“…In light of these findings, fractional exhaled NO (FeNO), representing airway NO, established as a marker of classic allergic asthma, has unclear significance in SCD . In a larger cohort of children from the SAC study, FeNO levels were associated with markers of atopy and future risk of ACS, but not with diagnosis of asthma, wheezing, pulmonary function, or BDR . The authors speculated that this may represent alternative forms of airway inflammation in SCD different from the classic pathways associated with atopic childhood asthma.…”